Leukoplakia is a clinical term rather than a definitive diagnosis that refers to a fixed white patch or plaque on the oral mucosa, assuming other causes have been excluded. Leukoplakia is an important risk factor for carcinomas of the oral mucosa and patients should be followed closely.

Leukoplakia is relatively common with a prevalence ranging from 0.5 to 1 %. It’s the most common pre-malignant lesion in the mouth. It tends to occur more often in men, appears after the 4^th decade, and increases in prevalence with age.

Potential causes of leukoplakia:

• tobacco smoking
• betel nut chewing
• alcohol
• poor oral hygiene
• trauma (e.g. biting)

Clinical features

Leukoplakia is usually a solitary, asymptomatic lesion, that begins as a well-demarcated, small white macule or papule. The lesion slowly enlarges, and may coalesce with other nearby lesions to form a larger plaque. It may appear homogeneous, or can be non-homogeneous with reticulated, or speckled areas. The surface may appear glistening, rough, or verrucous, with hyperkeratosis and erosions.

Red areas or papules in the mouth, called erythroplakia, can occur within lesions of leukoplakia or alone. Erythroplakia is analogous to leukoplakia, except it is much more common to harbour carcinoma in situ or invasive carcinoma.

Any part of the oral mucosa can be affected. The most commonly involved sites include the lower lip, buccal mucosa, edges of the tongue, and the floor of the mouth.

Malignant potential

Leukoplakia can become extensive oral plaques. Lesions tend to persist. The main concern is transformation to malignancy, which can occur up to 20 years later. Squamous cell carcinoma can appear in up to 1% of patients with leukoplakia per year. In erythroplakia, the transformation rate can be higher. Malignant transformation may be recognized by changes in the lesion such as local hardening with nodule formation and/or ulceration.

Differential diagnosis

As leukoplakia is a clinical diagnosis of exclusion, consider the following entities:

Pre-malignant/malignant

• actinic cheilitis — lips, chronic sun exposure
• squamous cell carcinoma — changing lesion, nodules

Infectious

• candidiasis — swab for yeast, and resolves with anti-fungal treatment
• oral hairy leukoplakia (Ebstein-Barr virus, immunocompromised patients)
  • white corrugated plaques on the sides of the tongue in patients with HIV

Inflammatory

• lichen planus — classic lesions elsewhere on body/scalp/nails
• lupus erythematosus — other signs of lupus

Hereditary

• white sponge nevus — mucosal keratin abnormality — onset in youth

Traumatic

• bite line — mid-buccal mucosa

Investigations

On history and physical exam, try to rule out other causes of white oral lesions (see differential diagnosis above). Perform a complete oral mucosal examination. Consider examining for lymphadenopathy of the head and neck.

Consider an immediate biopsy if high risk features for malignancy are present:

• rapid growth, large size
• prior history of oral squamous cell carcinoma
• tobacco, alcohol use

Most lesions of leukoplakia will require a biopsy. It’s important to rule out malignancy, such as squamous cell carcinoma, and to assess the degree of dysplasia. It can be very difficult to predict clinically which lesions are malignant, pre-malignant or benign. Typically those of leukoplakia show hyperkeratosis, minimal inflammation, with variable dysplasia. Pre-malignant lesions may show atypical cells that don’t extend the full-thickness of the epidermis; these represent 10-20% of cases.

Treatment

Consider the following behavioural modifications:

• smoking cessation
• avoid chewing tobacco
• excellent dental hygiene
• protect lips from sun exposure

Refer patients early to a dermatologist with any suspicious or changing oral lesion to consider biopsy and management.

Multiple treatment options are available and depend on the nature of the lesion. The more dysplasia present, the more aggressive the treatment.

If the biopsy shows epithelial dysplasia, complete removal is the main goal. With the following modalities, recurrences can range from 10-30%. Follow-up is necessary to ensure resolution.

• destructive therapies: cryotherapy, electrosurgery, CO₂ laser ablation
• topical: 5-fluorouracil, topical imiquimod
• combinations of destructive and topical therapies

If the biopsy shows squamous cell carcinoma, consider referral to a dermatologist or an ear nose and throat surgeon for excision of the lesion. Close clinical follow-up, including lymph node palpation, is warranted every 3-6 months to detect early recurrence or metastasis (e.g. lymph nodes, lungs). The threshold for repeat biopsies should be low.